Sweat chloride

Summary A 3-year-old Caucasian male has a history of chronic pulmonary and gastrointestinal problems and has a positive chloride sweat test. A family history of similar symptoms is also present. 

Sweat residues These contain fatty acids and sodium chloride, and increase the risk of corrosion after handling. Components should be washed in a solution of 5% water in methanol. 

Specific ion electrodes, similar in design to the glass electrode, have been developed to analyze for a variety of cations and anions. One of the first to be used extensively was a fluoride ion electrode that is sensitive to F- at concentrations as low as 0.1 part per million and hence is ideal for monitoring fluoridated water supplies. An electrode that is specific for Cl- ions is used to diagnose cystic fibrosis. Attached directly to the skin, it detects the abnormally high concentrations of sodium chloride in sweat that are a characteristic symptom of this disorder. Diagnoses that used to require an hour or more can now be carried out in a few minutes as a result, large numbers of children can be screened rapidly and routinely. 

Cystic fibrosis (CF) is a recessive genetic disorder prevalent among whites in North America and certain parts of northern Europe. It is characterized by chronic bacterial infections of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of the vas deferens, and elevated levels of chloride in sweat (> 60 mmol/L). 

Usually we think of solutions as liquids, and aqueous solutions are the most common liquid solutions in eveiyday life. Blood, sweat, and tears all are aqueous solutions. So are the beverages that we drink. The oceans are aqueous solutions of sodium chloride and other mineral salts. Even the fresh waters of streams and lakes are aqueous solutions containing salts and organic solutes. Most of this chapter discusses aqueous solutions. 

In addition to blood, certain types of specimens are submitted to the Pediatric laboratory which would not be commonly seen elsewhere. An example of this is sweat for analysis of chloride. The process of obtaining the sweat by iontophoresis usually falls to the personnel of the Laboratory of Neonatology (17). Stool for analysis of lipids and trypsin is more commonly submitted to the Laboratory of Neonatology than to the laboratory which services the adult population. The reason for this is that one is screening for certain intestinal diseases characteristic of infants and newborns which are rare in adults. Such conditions would be celiac disease, cystic fibrosis and others. 

Sodium chloride is a white, crystalline substance held together by the electrostatic forces between its two constituents, sodium ions and chloride ions. Salt is essential for human life. An average person has almost a quarter pound of it distributed throughout his or her body. Many of the sodium ions are found in the blood, where, among other things, they regulate blood pressure. Because salt is lost in sweat and urine, a normal diet requires us to consume it regularly. 

Abnormally high concentrations of sodium and chloride are found in sweat due to impaired reabsorption within the sweat duct from loss of CFTR channels. Patients are usually asymptomatic (other than a characteristic salty taste to the skin).2 In rare instances such as hot weather or excessive sweating during physical activity, patients may become dehydrated and experience symptoms of hyponatremia (nausea, headache, lethargy, and confusion). Similar CFTR defects are also seen in the salivary glands, manifested by increased saliva viscosity and impaired salivary function. 

Diagnosis of CF is based on two separate elevated sweat chloride concentrations of greater than or equal to 60 mEq/L (or mmol/L) obtained through pilocarpine iontophoresis (referred to as the sweat test ). Genetic testing (CFTR mutation analysis) may be performed to confirm the diagnosis, screen in utero, or detect carrier status. More than 70% of diagnoses are made by 12 months of age and almost all are made by age 12. 

A number of clinical symptoms characterize cystic fibrosis. Predominant among these is the presence of excess sodium chloride in cystic fibrosis patient sweat. Indeed, measurement of chloride levels in sweat remains the major diagnostic indicator of this disease. Another characteristic is the production of an extremely viscous, custard-like mucus in various body glands/organs that severely compromises their function. Particularly affected are ... 

It is believed that nickel penetrates the skin and acts as a hapten, complexing with selected peptide and/or amino-acid ligands to distort intercellular or cellular proteins, stimulating a type IV delayed (cell-mediated) hypersensitivity reaction [398]. Nickel water-soluble salts, like nickel chloride and nickel sulphate, are strong sensitizers [213, 215], The chloride induced in sweat is apparently an important factor in dissolving the metallic nickel, permitting the soluble nickel salts to act. 

Chloride ion-selective electrodes The most important region of application is the determination of chlorides in waters, including sea water (for a review, see [167]), in serum [110,112,371] (review in [167]) and in soil [151,219,341], The determination of chloride ions in sweat made screening for cystic fibrosis possible in new-born babies (review, [45,55a, 262]). Br , I and S " interfere in the determination of chlorides in phosphate rocks [81]. Sulphite can be determined directly using an electrode with an Hgj CI2 - HgS membrane [398] on the basis of the reaction... 

T. Bray, G. C. F. Clark, G. J. Moody and J. D. R. Thomas, A Perspective of Sodium and Chloride Ion-Selective Electrode Sweat Tests for Screening in Cystic Fibrosis, University of Wales, Cardiff (1975). 

Although most patch testing is done with nickel sulfate because it is less irritating than nickel chloride, exposure of the skin to nickel alloys results in the release of nickel chloride from the influence of human sweat. Therefore, nickel chloride is the more relevant form of nickel for examining threshold concentrations (Menne 1994). Menne and Calvin (1993) examined skin reactions to various concentrations of nickel chloride in 51 sensitive and 16 nonsensitive individuals. Although inflammatory reactions in the sweat ducts and hair follicles were observed at 0.01% and lower, positive reactions to nickel were not observed. To be scored as a positive reaction, the test area had to have both redness and infiltration, while the appearance of vesicles and/or a bullous reaction were scored as a more severe reaction. At 0.1%, 4/51 and 1/51 tested positive with and without 4% sodium lauryl sulfate. Menne et al. (1987) examined the reactivity to different nickel alloys in 173 nickel-sensitive individuals. With one exception (Inconel 600), alloys that released nickel into synthetic sweat at a rate of <0.5 pg/cmVweek showed weak reactivity, while alloys that released nickel at a rate of >1 pg/cm /week produced strong reactions. 

Anticholinergic side effects are categorized as peripheral or central. The most common peripheral side effects are dry mouth, decreased sweating, decreased bronchial secretions, blurred vision, difficulty with urination, constipation, and tachycardia. Bethanechol chloride, a cholinergic drug that does not cross the blood-brain barrier, may effectively treat these side effects at a dosage of 25-50 mg three times a day. 

Children with cystic fibrosis lose excessive amounts of salt in perspiration and become dehydrated readily. A salty taste of the skin and an elevated chloride concentration of sweat are traditional diagnostic symptoms.3 More serious problems arise from progressive respiratory failure and inadequate pancreatic secretion. Lung infections with Pseudomonas aeruginosa are the major cause of death. The CFTR gene is expressed in many tissues, especially those of the mucous membranes. 

ATP-dependent ABC transporter family. However, it is atypical because it also contains a regulated chloride channel) In secretory epithelia of intestines, pancreas, lungs, sweat glands, and kidneys Cl enters epithelial cells through their basolateral surfaces using an Na+ + K+ + 2 Cl cotransporter and exits the cells through their apical surfaces using the CFTR channel. Absorptive epithelia also contain both the cotransporter and the CFTR channel, but Cl flows into the cells from the exterior surface, and the distribution of the cotransporter and CFTR between basolateral and apical surfaces is opposite to that in secretory cells.1... 

Sweat is not just water but a dilute solution of electrolytes, mainly sodium and chloride. The actual composition varies from individual to individual and within individuals, according to circumstances. Typical values are shown in Table 13.6, from which it can be seen that sweat is considerably less concentrated than plasma. Hence sweating causes an increase in plasma electrolyte concentrations. Only in events of long duration (more than 3 h) is it considered essential to replace lost sodium during the event to guard against hyponatraemia (low plasma sodium concentration) (Gisolfi and Duchman, 1992). However, sports drinks conventionally contain added sodium, chloride and other electrolytes at levels similar to those found in sweat. 

For example, sodium ion is the principal cation of the extracellular fluid of the mammalian body, comprising, as the chloride and bicarbonate, more than 90% of the total solute in that fluid. Ingestion of sodium chloride solutions is used to replace salt lost by excessive perspiration. More sophisticated preparations have been proposed for this purpose one such preparation5 comprises mainly sodium chloride, supplemented with smaller amounts of potassium and phosphate ions to approximate the average composition of sweat in a sweetened glucose solution. 

Finally, the electrode configuration was tested with artificial sweat instead of sodium chloride-containing electrolyte solutions. No shifts of relationships or different results were found between the experiments performed with artificial sweat and those with sodium chloride solutions (section 10.4). From these results, the following conclusions can be drawn ... 

Sodium chloride in sweat determines the overall conductivity of the sweat. 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

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